The effect of oxidation on the degradation of photocrosslinkable alginate hydrogels.

Recently, we reported on a new photocrosslinkable alginate-based hydrogel, which has controllable physical and cell adhesive properties. The macromer solution containing cells can be injected in a minimally invasive manner into a defect site and crosslinked while maintaining high cell viability. The number of hydrolyzable ester bonds in the formed crosslinks may be controlled by altering the degree of methacrylation on the alginate polymer backbone. However, the degradation rate of the hydrogels has been found to be slower in vivo than in vitro. The purpose of this study was to develop photocrosslinked alginate hydrogels with an increased range of biodegradation rates for more rapid in vivo biodegradation in regenerative medicine and bioactive factor delivery applications. Therefore, we oxidized alginate prior to methacrylation to change the uronate residue conformations to an open-chain adduct, which makes it more vulnerable to hydrolysis. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of photocrosslinked hydrogels formed from oxidized, methacrylated alginates (OMAs) are tunable by varying the degree of alginate oxidation. The OMA macromers and photocrosslinked OMA hydrogels exhibited cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells (hBMMSCs). In addition, hMSCs derived from bone marrow or adipose tissue photoencapsulated within these hydrogels remained viable, and their proliferation rate was a function of alginate oxidation level and initial hydrogel weight fraction. Oxidation permits a wider range of photocrosslinked OMA hydrogels physical properties, which may enhance these therapeutic materials' utility in tissue engineering and other biomedical applications.

Biodegradable, photocrosslinked alginate hydrogels with independently tailorable physical properties and cell adhesivity.

Biocompatible polymers capable of photopolymerization are of immense interest for tissue engineering applications as they can be injected in a minimally invasive manner into a defect site and, then upon application of ultraviolet light, rapidly form hydrogels in situ. Cell adhesion interactions with a biomaterial are known to be important in regulating cell behaviors such as proliferation and differentiation. Therefore, we have covalently modified photocrosslinkable alginate with cell adhesion ligands containing the Arg-Gly-Asp amino acid sequence to form biodegradable, photocrosslinked alginate hydrogels with controlled cell adhesivity. This unique polymer system allows for independent modulation of the physical and biochemical signaling environment presented to cells. The physical properties of the hydrogels such as elastic moduli, swelling ratios, and degradation profiles were similar at the same crosslinking density regardless of the presence of adhesion ligands. Chondrocytes seeded on the surface of the adhesion ligand-modified hydrogels were able to attach and spread, whereas those seeded on unmodified hydrogels exhibited minimal adherence. Importantly, the adhesion-ligand-modified hydrogels enhanced the proliferation and chondrogenic differentiated function of encapsulated chondrocytes as demonstrated by increased DNA content and production of glycosaminoglycans compared to unmodified control hydrogels. This new photocrosslinkable, biodegradable biomaterial system in which the soluble (e.g., growth factors) and insoluble (e.g., cell adhesion ligands) biochemical signaling environment and the biomaterial physical properties (e.g., the elastic moduli) can be independently controlled may be a powerful tool for elucidating the individual and combined effects of these parameters on cell function for cartilage tissue engineering and other regenerative medicine applications.